Process for the preparation of sesquiterpene ketones

ABSTRACT

A process for the preparation of sesquiterpene ketones, which includes reacting, at 40* to 100*C. for from 6-12 hours, a sesquiterpene hydrocarbon having one olefinic linkage in the endocyclic position with hydrogen peroxide in the presence of a lower alkyl formate such as ethyl formate.

United States Patent [191 Boelens et a].

PROCESS FOR THE PREPARATION OF SESQUITERPENE KETONES Inventors: Harmannus Boelens, Huizen; Petrus C. Traas, Naarden, both of Netherlands Naarden International NV, Naarden-Bussum, Netherlands Filed: July 17, 1973 Appl. No.: 380,054

Assignee:

Foreign Application Priority Data July 20, 1972 United Kingdom 33960/72 US. Cl 260/586 P; 260/586 G; 260/586 F Int. Cl. C07c 45/04 Field of Search 260/587, 586 B, 586 P References Cited UNITED STATES PATENTS 6/1951 l-limel et al. 260/618 R June 3, 1975 3,647,847 3/1972 Curtis et al. ..260/587 3,718,698 2/1973 Hall ..260/587 Primary ExaminerBernard Helfin Assistant Examiner-Norman Morgenstern Attorney, Agent, or Firm-Stevens, Davis, Miller & Mosher 3 Claims, 4 Drawing Figures PATENTEU 3 AmcobmEv mc2m m m i 9 NF 2 9 m m w w m e m cm QN co ow 02. Dow com 009 00Ev coon 000m aauemwsuell PATENTEDJUH 3 I975 SHEET A oumtccm EE vtmm ucmEa m E2 086 52558. E

i 9 NF S 9 com com 009 wcocwcvmu *0 E5326 E aauemwsum Cedrene Thuyopsene lsolongifolene Delta -3carene PROCESS FOR THE PREPARATION OF SESQUITERPENE KETONES The invention relates to a process for the preparation of sesquiterpene ketones.

More particularly the invention provides a process for the oxydation of sesquiterpene hydrocarbons, containing a single ethylenic bond, with the aid of hydrogen peroxyde in such a way that sesquiterpene ketones free from isomeric ketones are obtained.

Although oxygen-containing sesquiterpene derivatives have found an increasing interest in the fragrance and flavour industry the number of sesquiterpene ketones actually used is still very small. S. Arctander, Perfume and Flavor Chemicals, Montclair, NJ. 1969) describes only cedranone (monograph no. 596), germacrone (no. 1463), nootkatone (no. 2382) and vetivone (no. 3089).

The increased interest is also reflected in some recent patent applications. The British Pat. Specification No. 1,197,579 discloses the use of an oxydation product of isolongifolene as an ingredient in perfume compositions.

The product is obtained by the oxydation of isolongifolene with sodium bichromate in acid medium and consists of a mixture of at least three ketones. Oxydation with hydrogen peroxyde and V in acetone again leads to a mixture of ketones together with unreacted isolongifolene. No yields have been mentioned.

The British Pat. Specification No. 1,216,048 covers the preparation and use as a fragrance material of novel thuyopsanones obtained from thuyopsene.

According to this patent application the oxydation of thuyopsene is preferentially performed with peracetic acid or chromylchloride but other reagents such as MnO KMnO, and oxygen in combination with actinic radiation may be used as well. The yield of thuyopsanone isomers obtained is 70% of the theoretical value in the case of peracids, whereas yields of 35.4% and 30% are obtained when chromylchloride or oxygen are used.

It has now been found that high yields of sesquiterpene ketones are obtained when suitable sesquiterpene hydrocarbons are reacted with hydrogen peroxyde in the presence of a lower alkylformate. No allylic oxydation occurs.

it is known from US. Pat. No. 2,555,927 that unsaturated organic compounds on treatment with hydrogen peroxyde and an alkyl formate boiling below 100C as a catalyst yield vicinal diols. The reaction applies to the hydroxylation of olefinic linkages in monoolefins, diolefins, unsaturated fatty acids, unsaturated alcohols, olefins substituted with a cyclic structure and to cyclic olefins which may be substituted by a saturated group.

In contrast to this it was found the sesquiterpene hydrocarbons C H containing one olefinic bond in endocyclic position, on treatment with hydrogen peroxyde and a lower alkyl formate, under reaction conditions which deviate from those claimed in US. Pat. No. 2.555.927, do not yield vicinal diols but give rise to the formation of sesquiterpene ketones.

Examples of sesquiterpene hydrocarbons -H which contain one olefinic linkage and follow the process of the invention are cedrenc. isolongifolene, thuyopsene and the like (formula 1. 2. and 3 rcsp.).

sesquiterpene hydrocarbons containing more than one olefinic linkage such as beta-caryophyllene. when reacted according to the invention. produce a mixture of unidentified compounds besides much polymeric material.

It was also found that sesquiterpene hydrocarbons containing one olefinic linkage in exocyclic position do not produce a carbonyl compound.

Comparison of related structures in the process of the invention, e.g. thuyopsene with delta-3-carene (formula 4) shows that with monoterpenes side reactions. such as opening of the cyclopropane ring and polymerisation. occur whereas the sesquiterpenes give a high yield of ketones.

The invention is therefore limited to sesquiterpene hydrocarbons containing one olefinic linkage in endocyclic position.

The preferred reaction conditions leading to diols according to US. Pat. No. 2,555,927 comprise the use per mol olefin of 1.1 -1.2 moles of hydrogen peroxyde of 5 15% by weight concentration combined with 50 mol based on hydrogen peroxyde, of low boiling alkyl formate, preferably methylformate, at a temperature in the range between 25 and 100C in a period between 12 and 48 hours.

For the introduction of a keto group into sesquiterpene hydrocarbons according to this invention the following conditions apply:

1 mol of sesquiterpene hydrocarbon is reacted with 1.3 1.5 moles of hydrogen peroxyde of a concentration of 20 -50% by weight, a lower alkylformate chosen from the group of methyl-, ethyl-, propyl-, and butylformates, preferably ethylformate, in an amount of -200 mol on hydrocarbon at a temperature in the range between 40 and 100C. in period between 6 and 12 hours.

The process of the invention may be illustrated by the following examples.

EXAMPLE 1 A 6-liter glass reactor, equiped with a stirrer a dropping-funnel and a reflux condenser, is charged with 1,350 g. isolongifolene (6.6 moles) and 975 g. ethyl formate (13.2 moles). The contents are heated to about 57C and 975 g. hydrogen peroxyde (concentration 30% by wt., 8.6 moles) is added at such rate that no excessive foaming occurs. This takes between 1 and 2 hours after which refluxing is continued for another 6 hours. During the reaction the temperature in the bottom gradually increases to about 73C. The reaction mass is then cooled to about 25C. and theaqueous bottomlayer drained off and discarded. The toplayer is washed in succession with 900 m1. saturated sodium bicarbonate solution and 900 ml. water and then dried over anhydrous magnesiumsulphate. On fractionation under vacuum 1014 g. isolongifolanone bp l131l7C/2 mm. n /D= 1,5011 lR-spectrum FIG. 2 is obtained.

A panel of six trained perfumers was unanimously of the opinion that the odour of the isolongifolanone thus obtained is preferred to that of the isomeric mixture of ketones known as isolongifolene oxidate from British Patent Specification No. 1,197,579.

EXAMPLE 11 In a similar 1 liter reactor 204 g. (1 mol) cedrene, 165 g 30% hydrogen peroxyde (1.45 moles) and g. ethyl formate are reacted as described in Example I. The temperature in the bottom increases from 58C to 82C in 6 hours. 154 g. cedranone bp 124 126C/O.2

3 mm; n /D 1.5026; IR-spectrum FIG. 2 is obtained.

EXAMPLE Ill Thuyopsene is reacted as in Example 11. Temperature increases from 57 to 78C in hours. 195 g. thuyopsanone is obtained. bp ll6-l22C/1.8 mm; Di /D 1,5022; lR-spectrum FIG. 3.

EXAMPLE IV The preparation according to example 111 is repeated, but ethyl formate is replaced by butyl formate (1,5 moles) 182 g thuyopanone is obtained.

The formulae 1 to 4 referred to herein are shown in FIG. 4 of the accompanying drawings. FIGS. 1 to 3 of the accompanying drawings show the infra-red spectra of the products of Examples 1 to 111, respectively.

What we claim is:

1. A process for the preparation of sesquiterpene ketones comprising reacting at a temperature of 40 to C. for a period of 6 to 12 hours 1 mol of sesquiterpene hydrocarbon having one olefinic linkage in an endocyclic position selected from the group consisting cedrene. isolongifolene and thuyopsene with 1.3 1.5 mols of hydrogen peroxide. having a concentration of from 20 50'/( by weight in the presence of from 200 mol 7c of a lower alkyl formate.

2. Process according to claim 1 wherein said lower alkyl formate is chosen from the group of methyl-. cthyl-, propyl-, and butylformates.

3. Process according to claim 2 wherein said lower 

1. A PROCESS FOR THE PREPARATION OF SESQUITERPENE KETONES COMPRISING REACTING AT A TEMPERATURE OF 40* TO 100*C. FOR A PERIOD OF 6 TO 12 HOURS 1 MOL OF SESQUITERPENE HYDROCARBON HAVING ONE OLEFINIC LINKAGE IN AN ENDOCYCLIC POSITION SELECTED FROM THE GROUP CONSISTING CEDRENE, ISOLONGIFOLENE AND THUYOPSENE WITH 1.3 - 1.5 MOLS OF HYDROGEN PEROXIDE, HAVING A CONCENTRATION OF FROM 20 - 50% BY WEIGHT IN THE PRESENCE OF FROM 120 - 200 MOL % OF A LOWER ALKYL FORMATE.
 1. A process for the preparation of sesquiterpene ketones comprising reacting at a temperature of 40* to 100*C. for a period of 6 to 12 hours 1 mol of sesquiterpene hydrocarbon having one olefinic linkage in an endocyclic position selected from the group consisting cedrene, isolongifolene and thuyopsene with 1.3 - 1.5 mols of hydrogen peroxide, having a concentration of from 20 - 50% by weight in the presence of from 120 - 200 mol % of a lower alkyl formate.
 2. Process according to claim 1 wherein said lower alkyl formate is chosen from the group of methyl-, ethyl-, propyl-, and butylformates. 